RESUMEN
Drug resistance is a significant challenge in cancer chemotherapy and is a primary factor contributing to poor recovery for cancer patients. Although drug-loaded nanoparticles have shown promise in overcoming chemotherapy resistance, they often carry a combination of drugs and require advanced design and manufacturing processes. Furthermore, they seldom approach chemotherapy-resistant tumors from an immunotherapy perspective. In this study, we developed a therapeutic nanovaccine composed solely of chemotherapy-induced resistant tumor antigens (CIRTAs) and the immune adjuvant Toll-like receptor (TLR) 7/8 agonist R848 (CIRTAs@R848). This nanovaccine does not require additional carriers and has a simple production process. It efficiently delivers antigens and immune stimulants to dendritic cells (DCs) simultaneously, promoting DCs maturation. CIRTAs@R848 demonstrated significant tumor suppression, particularly when used in combination with the immune checkpoint blockade (ICB) anti-PD-1 (αPD-1). The combined therapy increased the infiltration of T cells into the tumor while decreasing the proportion of regulatory T cells (Tregs) and modulating the tumor microenvironment, resulting in long-term immune memory. Overall, this study introduces an innovative strategy for treating chemotherapy-resistant tumors from a novel perspective, with potential applications in personalized immunotherapy and precision medicine.
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Vacunas contra el Cáncer , Desoxicitidina , Resistencia a Antineoplásicos , Gemcitabina , Inmunoterapia , Nanopartículas , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Desoxicitidina/farmacología , Animales , Inmunoterapia/métodos , Resistencia a Antineoplásicos/efectos de los fármacos , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Nanopartículas/química , Ratones , Humanos , Células Dendríticas/inmunología , Células Dendríticas/efectos de los fármacos , Línea Celular Tumoral , Ratones Endogámicos C57BL , Femenino , Imidazoles/farmacología , Imidazoles/uso terapéutico , Microambiente Tumoral/efectos de los fármacos , Antígenos de Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/inmunología , Neoplasias/tratamiento farmacológico , NanovacunasRESUMEN
Significant strides have been made in identifying tumour-associated antigens over the past decade, revealing unique epitopes crucial for targeted cancer therapy. Among these, the New York esophageal squamous cell carcinoma (NY-ESO-1) protein, a cancer/testis antigen, stands out. This protein is presented on the cell surface by major histocompatibility complex class I molecules and exhibits restricted expression in germline cells and various cancers, marking it as an immune-privileged site. Remarkably, NY-ESO-1 serves a dual role as both a tumour-associated antigen and its own adjuvant, implying a potential function as a damage-associated molecular pattern. It elicits strong humoural immune responses, with specific antibody frequencies significantly correlating with disease progression. These characteristics make NY-ESO-1 an appealing candidate for developing effective and specific immunotherapy, particularly for advanced stages of disease. In this review, we provide a comprehensive overview of NY-ESO-1 as an immunogenic tumour antigen. We then explore the diverse strategies for targeting NY-ESO-1, including cancer vaccination with peptides, proteins, DNA, mRNA, bacterial vectors, viral vectors, dendritic cells and artificial adjuvant vector cells, while considering the benefits and drawbacks of each strategy. Additionally, we offer an in-depth analysis of adoptive T-cell therapies, highlighting innovative techniques such as next-generation NY-ESO-1 T-cell products and the integration with lymph node-targeted vaccines to address challenges and enhance therapeutic efficacy. Overall, this comprehensive review sheds light on the evolving landscape of NY-ESO-1 targeting and its potential implications for cancer treatment, opening avenues for future tailored directions in NY-ESO-1-specific immunotherapy. HIGHLIGHTS: Endogenous immune response: NY-ESO-1 exhibited high immunogenicity, activating endogenous dendritic cells, T cells and B cells. NY-ESO-1-based cancer vaccines: NY-ESO-1 vaccines using protein/peptide, RNA/DNA, microbial vectors and artificial adjuvant vector cells have shown promise in enhancing immune responses against tumours. NY-ESO-1-specific T-cell receptor-engineered cells: NY-ESO-1-targeted T cells, along with ongoing innovations in engineered natural killer cells and other cell therapies, have improved the efficacy of immunotherapy.
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Antígenos de Neoplasias , Inmunoterapia , Proteínas de la Membrana , Neoplasias , Humanos , Antígenos de Neoplasias/inmunología , Inmunoterapia/métodos , Neoplasias/terapia , Neoplasias/inmunología , Proteínas de la Membrana/inmunología , Proteínas de la Membrana/uso terapéutico , Vacunas contra el Cáncer/uso terapéutico , Vacunas contra el Cáncer/inmunologíaRESUMEN
Despite the increasing number of studies on nanomedicine-based cancer immunotherapy, the overall research trends in this field remain inadequately characterized. This study aims to evaluate the research trends and hotspots in nanomedicine-based cancer immunotherapy through a bibliometric analysis. As of March 31, 2024, relevant publications were retrieved from the Web of Science Core Collection. Analytical tools including VOSviewer, CiteSpace, and an online bibliometric analysis platform were employed. A total of 5,180 publications were analyzed. The study reveals geographical disparities in research output, with China and the United States being the leading contributors. Institutionally, the Chinese Academy of Sciences, University of Chinese Academy of Sciences, and Sichuan University are prominent contributors. Authorship analysis identifies key researchers, with Liu Zhuang being the most prolific author. "ACS Nano" and the "Journal of Controlled Release and Biomaterials" are identified as the leading journals in the field. Frequently occurring keywords include "cancer immunotherapy" and "drug delivery." Emerging frontiers in the field, such as "mRNA vaccine," "sonodynamic therapy," "oral squamous cell carcinoma," "STING pathway,"and "cGAS-STING pathway," are experiencing rapid growth. This study aims to provide new insights to advance scientific research and clinical applications in nanomedicine-based cancer immunotherapy.
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Bibliometría , Inmunoterapia , Nanomedicina , Neoplasias , Humanos , Inmunoterapia/métodos , Neoplasias/terapia , Neoplasias/inmunología , Animales , Vacunas contra el Cáncer/uso terapéuticoRESUMEN
With the COVID-19 pandemic, the importance of vaccines has been widely recognized and has led to increased research and development efforts. Vaccines also play a crucial role in cancer treatment by activating the immune system to target and destroy cancer cells. However, enhancing the efficacy of cancer vaccines remains a challenge. Adjuvants, which enhance the immune response to antigens and improve vaccine effectiveness, have faced limitations in recent years, resulting in few novel adjuvants being identified. The advancement of artificial intelligence (AI) technology in drug development has provided a foundation for adjuvant screening and application, leading to a diversification of adjuvants. This article reviews the significant role of tumor vaccines in basic research and clinical treatment and explores the use of AI technology to screen novel adjuvants from databases. The findings of this review offer valuable insights for the development of new adjuvants for next-generation vaccines.
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Adyuvantes Inmunológicos , Inteligencia Artificial , COVID-19 , Vacunas contra el Cáncer , Neoplasias , Humanos , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Neoplasias/inmunología , Neoplasias/terapia , COVID-19/prevención & control , COVID-19/inmunología , SARS-CoV-2/inmunología , Animales , Desarrollo de Vacunas , Desarrollo de MedicamentosRESUMEN
BACKGROUND: Gliomas, particularly glioblastoma multiforme (GBM), are highly aggressive brain tumors that present significant challenges in oncology due to their rapid progression and resistance to conventional therapies. Despite advancements in treatment, the prognosis for patients with GBM remains poor, necessitating the exploration of novel therapeutic approaches. One such emerging strategy is the development of glioma vaccines, which aim to stimulate the immune system to target and destroy tumor cells. AIMS: This review aims to provide a comprehensive evaluation of the current landscape of glioma vaccine development, analyzing the types of vaccines under investigation, the outcomes of clinical trials, and the challenges and opportunities associated with their implementation. The goal is to highlight the potential of glioma vaccines in advancing more effective and personalized treatments for glioma patients. MATERIALS AND METHODS: This narrative review systematically assessed the role of glioma vaccines by including full-text articles published between 2000 and 2024 in English. Databases such as PubMed/MEDLINE, EMBASE, the Cochrane Library, and Scopus were searched using key terms like "glioma," "brain tumor," "glioblastoma," "vaccine," and "immunotherapy." The review incorporated both pre-clinical and clinical studies, including descriptive studies, animal-model studies, cohort studies, and observational studies. Exclusion criteria were applied to omit abstracts, case reports, posters, and non-peer-reviewed studies, ensuring the inclusion of high-quality evidence. RESULTS: Clinical trials investigating various glioma vaccines, including peptide-based, DNA/RNA-based, whole-cell, and dendritic-cell vaccines, have shown promising results. These vaccines demonstrated potential in extending survival rates and managing adverse events in glioma patients. However, significant challenges remain, such as therapeutic resistance due to tumor heterogeneity and immune evasion mechanisms. Moreover, the lack of standardized guidelines for evaluating vaccine responses and issues related to ethical considerations, regulatory hurdles, and vaccine acceptance among patients further complicate the implementation of glioma vaccines. DISCUSSION: Addressing the challenges associated with glioma vaccines involves exploring combination therapies, targeted approaches, and personalized medicine. Combining vaccines with traditional therapies like radiotherapy or chemotherapy may enhance efficacy by boosting the immune system's ability to fight tumor cells. Personalized vaccines tailored to individual patient profiles present an opportunity for improved outcomes. Furthermore, global collaboration and equitable distribution are critical for ensuring access to glioma vaccines, especially in low- and middle-income countries with limited healthcare resources CONCLUSION: Glioma vaccines represent a promising avenue in the fight against gliomas, offering hope for improving patient outcomes in a disease that is notoriously difficult to treat. Despite the challenges, continued research and the development of innovative strategies, including combination therapies and personalized approaches, are essential for overcoming current barriers and transforming the treatment landscape for glioma patients.
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Neoplasias Encefálicas , Vacunas contra el Cáncer , Glioma , Inmunoterapia , Animales , Humanos , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/terapia , Vacunas contra el Cáncer/uso terapéutico , Vacunas contra el Cáncer/inmunología , Glioma/inmunología , Glioma/terapia , Inmunoterapia/métodos , Inmunoterapia/tendenciasRESUMEN
Lymphoplasmacytic lymphoma (LPL) is an incurable low-grade lymphoma with no standard therapy. Nine asymptomatic patients treated with a first-in-human, neoantigen DNA vaccine experienced no dose limiting toxicities (primary endpoint, NCT01209871). All patients achieve stable disease or better, with one minor response, and median time to progression of 72+ months. Post-vaccine single-cell transcriptomics reveal dichotomous antitumor responses, with reduced tumor B-cells (tracked by unique B cell receptor) and their survival pathways, but no change in clonal plasma cells. Downregulation of human leukocyte antigen (HLA) class II molecules and paradoxical upregulation of insulin-like growth factor (IGF) by the latter suggest resistance mechanisms. Vaccine therapy activates and expands bone marrow T-cell clonotypes, and functional neoantigen-specific responses (secondary endpoint), but not co-inhibitory pathways or Treg, and reduces protumoral signaling by myeloid cells, suggesting favorable perturbation of the tumor immune microenvironment. Future strategies may require combinations of vaccines with agents targeting plasma cell subpopulations, or blockade of IGF-1 signaling or myeloid cell checkpoints.
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Vacunas contra el Cáncer , Macroglobulinemia de Waldenström , Humanos , Masculino , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Vacunas contra el Cáncer/administración & dosificación , Persona de Mediana Edad , Femenino , Macroglobulinemia de Waldenström/inmunología , Macroglobulinemia de Waldenström/terapia , Macroglobulinemia de Waldenström/genética , Anciano , Microambiente Tumoral/inmunología , Medicina de Precisión/métodos , Vacunas de ADN/inmunología , Vacunas de ADN/uso terapéutico , Antígenos de Neoplasias/inmunología , Linfocitos B/inmunologíaAsunto(s)
Neoplasias del Sistema Nervioso Central , Humanos , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Inmunoterapia Adoptiva , Proyectos Piloto , Productos Biológicos/uso terapéutico , Vacunas contra el Cáncer/uso terapéutico , Linfoma/tratamiento farmacológico , Linfoma/diagnósticoRESUMEN
Gliomas are one of the most aggressive types of brain tumors and are associated with high morbidity and mortality rates. Currently, conventional treatments for gliomas such as surgical resection, radiotherapy, and chemotherapy have limited effectiveness, and new approaches are needed to improve patient outcomes. mRNA-based vaccines represent a promising therapeutic strategy for cancer treatment, including gliomas. Recent advances in immunotherapy using mRNA-based dendritic cell vaccines have shown great potential in preclinical and clinical trials. Dendritic cells are professional antigen-presenting cells that play a crucial role in initiating and regulating immune responses. In this review, we summarize the current progress of mRNA-based vaccines for gliomas, with a focus on recent advances in dendritic cell-based mRNA vaccines. We also discuss the feasibility and safety of mRNA-based clinical applications for gliomas.
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Neoplasias Encefálicas , Vacunas contra el Cáncer , Células Dendríticas , Glioma , ARN Mensajero , Humanos , Glioma/terapia , Glioma/inmunología , Glioma/genética , Vacunas contra el Cáncer/uso terapéutico , Vacunas contra el Cáncer/inmunología , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/genética , Células Dendríticas/inmunología , ARN Mensajero/genética , ARN Mensajero/uso terapéutico , ARN Mensajero/inmunología , Inmunoterapia/métodos , Animales , Vacunas de ARNmRESUMEN
Immunotherapy has shown promising therapeutic effects in hematological malignancies and certain solid tumors and has emerged as a critical and highly potential treatment modality for cancer. However, prostate cancer falls under the category of immune-resistant cold tumors, for which immunotherapy exhibits limited efficacy in patients with solid tumors. Thus, it is important to gain a deeper understanding of the tumor microenvironment in prostate cancer to facilitate immune system activation and overcome immune suppression to advance immunotherapy for prostate cancer. In this review, we discuss the immunosuppressive microenvironment of prostate cancer, which is characterized by the presence of few tumor-infiltrating lymphocytes, abundant immunosuppressive cells, low immunogenicity, and a noninflammatory phenotype, which significantly influences the efficacy of immunotherapy for prostate cancer. Immunotherapy is mainly achieved by activating the host immune system and overcoming immunosuppression. In this regard, we summarize the therapeutic advances in immune checkpoint blockade, immunogenic cell death, reversal of the immunosuppressive tumor microenvironment, tumor vaccines, immune adjuvants, chimeric antigen receptor T-cell therapy, and overcoming penetration barriers in prostate cancer, with the aim of providing novel research insights and approaches to enhance the effectiveness of immunotherapy for prostate cancer.
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Vacunas contra el Cáncer , Inmunoterapia , Neoplasias de la Próstata , Microambiente Tumoral , Humanos , Masculino , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/patología , Microambiente Tumoral/inmunología , Inmunoterapia/métodos , Vacunas contra el Cáncer/uso terapéutico , Vacunas contra el Cáncer/inmunología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , AnimalesRESUMEN
Cancer prevention encompasses both screening strategies to find cancers early when they are likely to be most treatable and prevention and interception strategies to reduce the risk of developing cancers. Bioconjugates, here defined broadly as materials and molecules that have synthetic and biological components, have roles to play across the cancer-prevention spectrum. In particular, bioconjugates may be developed as affordable, accessible, and effective screening strategies or as novel vaccines and drugs to reduce one's risk of developing cancers. Developmental programs are available for taking novel technologies and evaluating them for clinical use in cancer screening and prevention. While a variety of different challenges exist in implementing cancer-prevention interventions, a thoughtful approach to bioconjugates could improve the delivery and acceptability of the interventions.
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Neoplasias , Humanos , Neoplasias/prevención & control , Vacunas contra el Cáncer/uso terapéutico , AnimalesRESUMEN
Current treatment outcome of patients with glioblastoma (GBM) remains poor. Following standard therapy, recurrence is universal with limited survival. Tumors from 173 GBM patients are analysed for somatic mutations to generate a personalized peptide vaccine targeting tumor-specific neoantigens. All patients were treated within the scope of an individual healing attempt. Among all vaccinated patients, including 70 treated prior to progression (primary) and 103 treated after progression (recurrent), the median overall survival from first diagnosis is 31.9 months (95% CI: 25.0-36.5). Adverse events are infrequent and are predominantly grade 1 or 2. A vaccine-induced immune response to at least one of the vaccinated peptides is detected in blood samples of 87 of 97 (90%) monitored patients. Vaccine-specific T-cell responses are durable in most patients. Significantly prolonged survival is observed for patients with multiple vaccine-induced T-cell responses (53 months) compared to those with no/low induced responses (27 months; P = 0.03). Altogether, our results highlight that the application of personalized neoantigen-targeting peptide vaccine is feasible and represents a promising potential treatment option for GBM patients.
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Neoplasias Encefálicas , Vacunas contra el Cáncer , Glioblastoma , Medicina de Precisión , Vacunas de Subunidades Proteicas , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antígenos de Neoplasias/inmunología , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/terapia , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Glioblastoma/inmunología , Glioblastoma/terapia , Medicina de Precisión/métodos , Vacunas de Subunidades Proteicas/inmunología , Vacunas de Subunidades Proteicas/uso terapéutico , Linfocitos T/inmunología , Resultado del TratamientoRESUMEN
Targeted therapies and immunotherapies have radically improved treatment for advanced non-small-cell lung cancer (NSCLC). Tyrosine kinase inhibitors targeting oncogenic driver mutations continue to evolve over multiple generations to enhance effectiveness and tackle drug resistance. Immune checkpoint inhibitors remain integral for the treatment of NSCLCs that do not have specific actionable genetic mutations. Antibody-drug conjugates and bispecific antibodies are being integrated into treatment guidelines, and emerging therapies include T-cell engagers, cellular therapies, cancer vaccines, and external devices. Despite these advances, challenges remain in identifying predictive biomarkers to individually tailor treatments, abrogate resistance, reduce costs, and ensure optimal cancer treatment accessibility.
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Carcinoma de Pulmón de Células no Pequeñas , Inmunoterapia , Neoplasias Pulmonares , Humanos , Anticuerpos Biespecíficos/uso terapéutico , Vacunas contra el Cáncer/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/terapia , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia/métodos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/terapia , Terapia Molecular Dirigida , /uso terapéuticoRESUMEN
OBJECTIVES: To determine if nutritional status effects response to immunotherapy in women with gynecologic malignancies. METHODS: A retrospective chart review was conducted on gynecologic cancer patients who received immunotherapy at a single institution between 2015 and 2022. Immunotherapy included checkpoint inhibitors and tumor vaccines. The prognostic nutritional index (PNI) was calculated from serum albumin levels and total lymphocyte count. PNI values were determined at the beginning of treatment for each patient and assessed for their association with immunotherapy response. Disease control response (DCR) as an outcome of immunotherapy was defined as complete response, partial response, or stable disease. RESULTS: One hundred and ninety-eight patients received immunotherapy (IT) between 2015 and 2022. The gynecological cancers treated were uterine (38%), cervix (32%), ovarian (25%), and vulvar or vaginal (4%) cancers. The mean PNI for responders was higher than the non-responder group (p < 0.05). The AUC value for PNI as a predictor of response was 49. A PNI value of 49 was 43% sensitive and 85% specific for predicting a DCR. In Cox proportional hazards analysis, after adjusting for ECOG score and the number of prior chemotherapy lines, severe malnutrition was associated with progression-free survival (PFS) (HR = 1.85, p = 0.08) and overall survival (OS) (HR = 3.82, p < 0.001). Patients with PNI < 49 were at a higher risk of IT failure (HR = 2.24, p = 0.0001) and subsequent death (HR = 2.84, p = 9 × 10-5). CONCLUSIONS: PNI can be a prognostic marker to predict response rates of patients with gynecologic cancers treated with immunotherapy. Additional studies needed to understand the mechanistic role of malnutrition in immunotherapy response.
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Neoplasias de los Genitales Femeninos , Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Estado Nutricional , Humanos , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias de los Genitales Femeninos/terapia , Neoplasias de los Genitales Femeninos/inmunología , Anciano , Inmunoterapia/métodos , Adulto , Evaluación Nutricional , Resultado del Tratamiento , Anciano de 80 o más Años , Vacunas contra el Cáncer/uso terapéutico , Vacunas contra el Cáncer/administración & dosificaciónRESUMEN
GBM is the most common, aggressive, and intracranial primary brain tumor; it originates from the glial progenitor cells, has poor overall survival (OS), and has limited treatment options. In this decade, GBM immunotherapy is in trend and preferred over several conventional therapies, due to their better patient survival outcome. This review explores the clinical trials of several immunotherapeutic approaches (immune checkpoint blockers (ICBs), CAR T-cell therapy, cancer vaccines, and adoptive cell therapy) with their efficacy and safety. Despite significant progress, several challenges (viz., immunosuppressive microenvironment, heterogeneity, and blood-brain barrier (BBB)) were experienced that hamper their immunotherapeutic potential. Furthermore, these challenges were clinically studied to be resolved by multiple combinatorial approaches, discussed in the later part of the review. Thus, this review suggests the clinical use and potential of immunotherapy in GBM and provides the holistic recent knowledge and future perspectives.
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Neoplasias Encefálicas , Glioblastoma , Inmunoterapia , Microambiente Tumoral , Humanos , Inmunoterapia/métodos , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/inmunología , Glioblastoma/terapia , Glioblastoma/inmunología , Microambiente Tumoral/inmunología , Vacunas contra el Cáncer/uso terapéutico , Vacunas contra el Cáncer/inmunología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Animales , Barrera Hematoencefálica/inmunologíaRESUMEN
Background: Glioblastoma (GBM) is a poor prognosis grade 4 glioma. After surgical resection, the standard therapy consists of concurrent radiotherapy (RT) and temozolomide (TMZ) followed by TMZ alone. Our previous data on melanoma patients showed that Dendritic Cell vaccination (DCvax) could increase the amount of intratumoral-activated cytotoxic T lymphocytes. Methods: This is a single-arm, monocentric, phase II trial in two steps according to Simon's design. The trial aims to evaluate progression-free survival (PFS) at three months and the safety of a DCvax integrated with standard therapy in resected GBM patients. DCvax administration begins after completion of RT-CTwith weekly administrations for 4 weeks, then is alternated monthly with TMZ cycles. The primary endpoints are PFS at three months and safety. One of the secondary objectives is to evaluate the immune response both in vitro and in vivo (DTH skin test). Results: By December 2022, the first pre-planned step of the study was concluded with the enrollment, treatment and follow up of 9 evaluable patients. Two patients had progressed within three months after leukapheresis, but none had experienced DCvax-related G3-4 toxicities Five patients experienced a positive DTH test towards KLH and one of these also towards autologous tumor homogenate. The median PFS from leukapheresis was 11.3 months and 12.2 months from surgery. Conclusions: This combination therapy is well-tolerated, and the two endpoints required for the first step have been achieved. Therefore, the study will proceed to enroll the remaining 19 patients. (Eudract number: 2020-003755-15 https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-003755-15/IT).
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Neoplasias Encefálicas , Vacunas contra el Cáncer , Células Dendríticas , Glioblastoma , Humanos , Glioblastoma/terapia , Glioblastoma/inmunología , Glioblastoma/mortalidad , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Vacunas contra el Cáncer/administración & dosificación , Vacunas contra el Cáncer/efectos adversos , Células Dendríticas/inmunología , Células Dendríticas/trasplante , Persona de Mediana Edad , Femenino , Masculino , Adulto , Anciano , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/mortalidad , Temozolomida/uso terapéutico , Temozolomida/administración & dosificación , Supervivencia sin ProgresiónRESUMEN
BACKGROUND: Targeting kinases presents a potential strategy for treating solid tumors; however, the therapeutic potential of vaccines targeting kinases remains uncertain. METHODS: Adenovirus (Ad) vaccines encoding Aurora kinase A (AURKA) or cyclin-dependent kinase 7 (CDK7) were developed, and their therapeutic potentials were investigated by various methods including western blot, flow cytometry, cytotoxic T lymphocyte assay, and enzyme-linked immunospot (ELISpot), in mouse and humanized solid tumor models. RESULTS: Co-immunization with Ad-AURKA/CDK7 effectively prevented subcutaneous tumor growth in the Renca, RM-1, MC38, and Hepa1-6 tumor models. In therapeutic tumor models, Ad-AURKA/CDK7 treatment impeded tumor growth and increased immune cell infiltration. Administration of Ad-AURKA/CDK7 promoted the induction and maturation of dendritic cell subsets and augmented multifunctional CD8+ T-cell antitumor immunity. Furthermore, the vaccine induced a long-lasting antitumor effect by promoting the generation of memory CD8+ T cells. Tumor recovery on CD8+ T-cell depletion underscored the indispensable role of these cells in the observed therapeutic effects. The potent efficacy of the Ad-AURKA/CDK7 vaccine was consistently demonstrated in lung metastasis, orthotopic, and humanized tumor models by inducing multifunctional CD8+ T-cell antitumor immune responses. CONCLUSIONS: Our findings illustrate that the Ad-AURKA/CDK7 vaccine targeting dual kinases AURKA and CDK7 emerges as a promising and effective therapeutic approach for the treatment of solid tumors.
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Aurora Quinasa A , Vacunas contra el Cáncer , Animales , Ratones , Humanos , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Adenoviridae , Línea Celular Tumoral , Quinasa Activadora de Quinasas Ciclina-Dependientes , Femenino , Neoplasias/inmunología , Neoplasias/terapia , Vacunas contra el Adenovirus/inmunología , Vacunas contra el Adenovirus/uso terapéutico , Linfocitos T CD8-positivos/inmunologíaRESUMEN
Cancer immunotherapy activates the host immune system against tumor cells and has the potential to lead to the development of innovative strategies for cancer treatment. Neoantigens are non-self-antigens produced by genetic mutations in tumor cells that induce a strong immune response against tumor cells without central immune tolerance. Along with advances in neoantigen analysis technology, the development of vaccines focusing on neoantigens is being accelerated. Whereas there are various platforms for neoantigen vaccines, combined immuno-therapies are being developed simultaneously with the clinical application of synthetic long peptides and mRNA and dendritic-cell (DC)-based vaccines. Personalized DC-based vaccines not only can load various antigens including neoantigens, but also have the potential to elicit a strong immune response in T cells as antigen-presenting cells. In this review, we describe the properties of neoantigens and the basic characteristics of DCs. We also discuss the clinical applications of neoantigen vaccines, focusing on personalized DC-based vaccines, as well as future research and development directions and challenges.
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Antígenos de Neoplasias , Vacunas contra el Cáncer , Células Dendríticas , Neoplasias , Medicina de Precisión , Humanos , Células Dendríticas/inmunología , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Antígenos de Neoplasias/inmunología , Neoplasias/inmunología , Neoplasias/terapia , Medicina de Precisión/métodos , Inmunoterapia/métodos , AnimalesRESUMEN
Multiple myeloma (MM) is a hematological cancer marked by plasma cell accumulation in the bone marrow. Despite treatment advancements, MM remains incurable in most patients. MM-associated immune dysregulation fosters disease progression, prompting research into immunotherapy to combat the disease. An area of immunotherapy investigation is the design of myeloma vaccine therapy to reverse tumor-associated immune suppression and elicit tumor-specific immune responses to effectively target MM cells. This article reviews vaccine immunotherapy for MM, categorizing findings by antigen type and delivery method. Antigens include idiotype (Id), tumor-associated (TAA), tumor-specific (TSA), and whole tumor lysate. Myeloma vaccination has so far shown limited clinical efficacy. However, further studies are essential to optimize various aspects, including antigen and patient selection, vaccine timing and sequencing, and rational combinations with emerging MM treatments.